Diagn Interv Radiol 2014; 20:323-329
INTERVENTIONAL RADIOLOGY
© Turkish Society of Radiology 2014
ORIGINAL ARTICLE
The effect of using different embolic agents on survival in
transarterial chemoembolization of hepatocellular carcinoma:
gelfoam versus polyvinyl alcohol
Ali Koçyiğit, Oğuz Dicle, Yiğit Göktay, İbrahim Astarcıoğlu
PURPOSE
We aimed to compare the effect of using different embolic agents such as gelfoam and polyvinyl alcohol (PVA) on
survival, tumor response, and complications in transarterial chemoembolization (TACE) of hepatocellular carcinoma
(HCC) patients.
MATERIALS AND METHODS
We retrospectively reviewed the medical records of 38 inoperable HCC patients who underwent TACE between August
1998 and April 2007. A total of 50 TACE sessions were performed using PVA (n=18) or gelfoam particles (n=20), following the application of 60 mg doxorubicin with 10–20 mL lipiodol emulsion. The PVA and gelfoam groups were compared
based on clinical, laboratory, and demographic variables. Survival rates were calculated starting from the first TACE session
using the Kaplan-Meier analysis.
RESULTS
There was no significant difference between the survival rates
of PVA and gelfoam groups (P = 0.235). Overall survival rates
at 12, 24, 36, 48, and 60 months were 55%, 36%, 15%, 7%,
and 5%, respectively. Tumor response, age, lipiodol accumulation type, number of HCC foci, complications, and serum
alpha-fetoprotein level were significant factors for survival in
all patients.
CONCLUSION
Use of gelfoam or PVA as the embolic agent did not have a
significant impact on survival. Complete tumor response, intensive lipiodol accumulation in tumor, older age (>60 years),
fewer (≤3) HCC foci, and low serum alpha-fetoprotein level
(≤400 ng/mL) were found to improve cumulative survival
significantly.
From the Department of Radiology (A.K.  [email protected]),
Pamukkale University School of Medicine, Denizli, Turkey; the
Department of Radiology (O.D., Y.G.), Dokuz Eylül University School
of Medicine, İzmir, Turkey; the Department of General Surgery
(İ.A.), Dokuz Eylül University School of Medicine, İzmir, Turkey.
Received 18 November 2013; revision requested 9 December 2013; revision
received 13 December 2013; accepted 18 December 2013.
Published online 29 April 2014.
DOI 10.5152/dir.2014.13462
H
epatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and the third leading cause of cancer
death worldwide. More than 90% of HCC occurs following liver
cirrhosis (1). Transplantation, ablative treatments, and surgical resection are considered as curative treatments (2). Unfortunately, only 30%
of HCC cases are eligible for these curative treatments at the time of
diagnosis, while the majority is diagnosed in advanced stage, beyond
the criteria for surgical therapy (3, 4). Transarterial chemoembolization
(TACE) remains the most widely used and established palliative treatment in the management of patients with advanced HCC, with proven
survival benefits over the best supportive care (5−8). Despite the worldwide acceptance of TACE in the treatment of surgically unresectable
HCC, there is still no standard protocol for its use (9). Various TACE
techniques which comprise selective or superselective catheterization,
different chemotherapeutic regimens (doxorubicin, 5-fluorouracil, cisplatin, mytomycin-c, epirubicin, neocarzinostatin), and different embolization agents can influence the patient outcome (10, 11). Furthermore
a previous review stated that polyvinyl alcohol (PVA) particles may be
better than gelatin sponge in TACE treatment (12). Thus, the primary
aim of our study was to compare the effect of different embolic agents
such as PVA and gelfoam on survival and patient outcome in the treatment of surgically unresectable HCC. The secondary aim was to investigate the effect of TACE on survival.
Materials and methods
Patient selection
We retrospectively reviewed 38 HCC patients (28 men, 10 women;
mean age, 62.8±12.4 years) who underwent TACE between August 1998
and April 2007 in our institution. The study protocol was approved by
the local ethics committee, and all patients gave a written informed consent before the procedure. Patients with surgically unresectable HCC
were evaluated by an oncology board and underwent TACE procedure
upon the decision of this board. Patients with surgically unresectable
HCC, with or without portal branch throm­bosis, and without previous
TACE treatment were included in the study. Patients with main portal
vein throm­bosis, hepatic failure, or extrahepatic metastasis were excluded. History of concomittant radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI) was not a criterion for exclusion. Doxorubicin (60 mg) with lipiodol emulsion (10−20 mL) was administered to all
patients before embolization. Twenty patients underwent embolization
with gelfoam and 18 patients underwent embolization with PVA. Two
patients in gelfoam group had previous PEI and RFA treatments. Two pa323
tients in the gelfoam group underwent
additional PEI, and two patients in the
PVA group underwent additional RFA.
Medical records were obtained from
the hospital information system, and
radiological data were retrieved using
the picture archiving and communication system.
Chemoembolization procedure and
technique
All patients underwent triple phase
multidetector CT (unenhanced, arterial and venous phases) within a month
before the TACE session. CT examinations were performed using a 16-detector CT (Brilliance 16, Philips Medical
Systems, Best, the Netherlands) in supine position. Axial scanning parameters were as follows: tube voltage,
120 kV; mAs, 300; collimation, 16×1.5
mm; matrix, 512×512; rotation time,
0.75 s; pitch, 0.93; FOV, 40 cm; slice
thickness, 5 mm.
All patients were preprocedurally
starved at least eight hours and hydrated with 150−200 mL/h of normal saline solution. TACE was performed by
interventional radiologists (O.D. and
A.Y.G.) who had similar experience
and expertise in the management of
HCC. Superior mesenteric angiography
was performed to determine the portal venous patency and possible right
hepatic arterial variations. Then, right
and left hepatic angiography was performed to determine the tumor-bearing artery for drug administration.
After selective or superselective catheterization of the distal feeding artery
with a microcatheter (Progreat, Terumo, Tokyo, Japan), doxorubicin (Adriblastine, Pfizer, Nerviano, Italy) (1 mg/
kg of weight, maximum 60 mg) mixed
with 10−20 mL of iodized oil emulsion
(Lipiodol, Guerbet, Aulnay-sous-Bois,
France) and 10 mL of contrast agent
(Ultravist 300/100 mL Bayer Schering
Pharma, Berlin, Germany) was administered in all patients before the embolization step. After the administration
of lipiodol chemotherapy, embolization was performed using 1−2 mm diameter gelfoam particles (Gelitaspon,
Gelita Medical BV, Amsterdam, the
Netherlands) or 150−250 µm PVA particles. Injection of lipiodol chemotherapy and embolization were performed
under realtime floroscopy to avoid the
reflux of the injected material. When
the flow slowed down significantly
with stagnation, embolization was
stopped for a while to allow flow restoration. Then embolization was reinstated until complete occlusion of the
feeding artery was achieved.
Tumor response assessment
Tumor response was assessed on
multiphase contrast-enhanced CT, one
month after the TACE session. In one
patient follow-up imaging was performed by magnetic resonance imaging (MRI) due to renal functional disorder. An abdominal radiologist with
a six-year experience, who was blinded
to TACE technique, reviewed the CT
and MRI data. We used the modified
RECIST criteria (13, 14) to assess the
tumor response as follows: complete
response, elimination of any intratumor arterial enhancement in all target
lesions; partial response, at least 30%
decrease in the sum of the largest diameters of viable target lesions; stable
disease, any cases which do not qualify
for either partial response or progressive disease; and progressive disease,
at least 20% increment in the sum of
the largest diameters of viable target
lesions. Progressive disease was also
noted when one or more new lesions
were detected. Viable lesions were defined by the presence of an enhanced
area inside the tumor at arterial phase.
Lipiodol deposition was also semiquantitatively assessed by opacification on unenhanced CT. Four types
of lipiodol deposition were defined as
follows: type 1, diffuse homogeneous
opacification of the tumor focus; type
2, mostly homogeneous opacification;
type 3, weak heterogeneous opacification; type 4, very weak or no opacification of the tumor focus (15).
Additional TACE session was performed if tumor enhancement was
determined on follow-up CT. TACE
session was performed twice in 10 patients (26.3%), and three times in six
patients (15.8%). If there was no enhancement of the tumor, patients underwent screening with repeat CT imaging performed every three months.
Assessment parameters
Potential prognostic factors of tumor
response and survival were analyzed,
324 • July–August 2014 • Diagnostic and Interventional Radiology
including patient characteristics such
as age and gender, cirrhosis etiology,
serum alanine and aspartate aminotransferases, total serum bilirubin, albumin, prothrombin time, Child-Pugh
class, Okuda class; tumor characteristics such as tumor size and number,
portal vein thrombosis, serum alpha-fetoprotein (AFP); procedure-related factors such as TACE technique,
type of embolization agent; short-term
post-therapeutic evaluation such as
postembolization syndrome, tumor
response, tumor lipiodol fixation, liver
failure, and long-term evaluation such
as the number of TACE sessions, and
the date of death.
Statistical analysis
Overall survival was evaluated by
Kaplan-Meier curves and compared
between groups using the log rank
test. The univariate analysis for overall survival was performed using the
log-rank test on Kaplan-Meier curves
for categorical variables and the univariate Cox Model for continuous
variables. Results were expressed as
mean±standard deviation. Chi-square
and Mann-Whitney U tests were used
in comparison of categorical and continuous variables, respectively.
To determine factors affecting survival, continuous variables and some
multinomial categorical variables were
dichotomized as follows: percentage of
hepatic involvement ≤50% vs. >50%,
tumor diameter ≤5 cm vs. >5 cm, number of HCC foci ≤3 vs. >3, aspartate
aminotransferase level ≤63 U/L vs. >63
U/L, AFP level ≤400 ng/mL vs. >400
ng/mL, age ≤60 years vs. >60 years
(16), number of TACE sessions ≤1 and
>1, type of lipiodol accumulation (type
1 vs. the other types), type of tumor response (type 4 vs. the other types).
A P value less than 0.05 was considered as statistically significant. The
statistical software used was Statistical
Package for Social Sciences, version 17
(SPSS Inc., Chicago, Illinois, USA).
Results
Thirty-eight patients underwent
TACE treatment in the study period;
all subjects died in the course of the
study. One patient underwent liver
transplantation in the follow-up period, but he died right after the transKoçyiğit et al.
plantation surgery. Overall survival
rates for the whole study group was
55%, 36%, 15%, 7%, and 5% at 12,
24, 36, 48, and 60 months respectively. Mean survival of the whole group
was 18.7±18.2 months (range, 1–72
months).
The gelfoam and PVA groups were
similar in all factors except in ChildPugh and Okuda classification (Table
1). The PVA group had significantly more patients in Child-Pugh A (P
= 0.01) and Okuda class I (P = 0.04).
However this result did not effect the
duration of follow-up (P = 0.79) or the
survival rates of the two groups (P =
0.235). Survival rates at 12, 24, 36, 48
and 60 months were 66%, 44%, 16%,
11%, and 5% for PVA the group and
45%, 30%, 15%, 5%, and 5% for the
gelfoam group (Figure).
A total of 60 TACE sessions (mean,
1.5) were performed in 38 patients.
Twenty patients in the gelfoam group
underwent 29 sessions (mean, 1.4) and
18 patients in the PVA group underwent 31 sessions (mean, 1.7) (P = 0.18).
Prognostic factor analysis for survival is shown in Table 2. Patients with ≤3
HCC nodules (n=29) had significantly better survival than patients with
>3 HCC nodules (n=9); survival rates
at 12, 24, 36, 48 and 60 months were
58%, 44%, 20%, 10%, and 6% for patients with ≤3 HCC nodules and 44%,
11%, 0%, 0%, and 0% for patients with
>3 HCC nodules (P = 0.023); mean survival was 21 months and nine months,
respectively.
Patients with AFP levels ≤400 ng/mL
(n=31) had significantly better survival than patients with AFP levels >400
ng/mL (n=7); survival at 12, 24, 36, 48
and 60 months were 64%, 45%, 19%,
9%, and 6% for patients with AFP ≤400
ng/mL and 14%, 0%, 0%, 0%, and 0%,
for patients with AFP >400 ng/mL (P <
0.001); mean survival was 31 months
and 17 months, respectively.
Ten patients developed complications
other than postembolectomy syndrome
after the TACE session. Of these, four
patients died due to hepatic failure
within 30 days, and one patient died
due to gastrointestinal bleeding within
three days after the TACE, leading to
an overall mortality rate of 13%. Two
of these five patients were in the gelfoam group (10% of that group); both
Table 1. Characteristics of patients undergoing the TACE procedure
Total
Patients, n
Age (years), mean±SD
Male gender, %
PVAGelfoam
P
38 1820
62.8±12.4
73.7
61±15
77.8
63±9.20.83
700.35
Etiology, %0.36
HBV
47.4
55.6
40
HCV
39.5
33.3
45
Other
13.2
11.1
15
Child-Pugh class, %0.01
A
52.6
77.8
30
B
39.5
11.1
65
C
7.9
11.1
5
Okuda class, %0.04
I
44.7
66.7
25
II
47.4
22.2
70
III
7.9
11.1
5
Maximum HCC size (mm), mean±SD 63.3±45.5
64±53.8
62.8±380.48
Number of HCC foci, mean±SD
2.1±1.2
1.9±1.2
2.3±1.20.37
Bilirubin (mg/dL), mean±SD
2.4±2.1
2.5±3
2.3±0.70.18
Albumin (g/dL), mean±SD
3.2±0.7
3.4±0.7
3.0±0.70.07
AST (U/L), mean±SD
101.9±145.1105.7±173.9 98.5±118 0.35
ALT (U/L), mean±SD
100.3±200.5126.4±282.5 76.9±75.30.69
AFP (ng/mL), mean±SD
794±3269 210.2±331.3 1319±44830.95
PT (s), mean±SD
15.9±4.9
14.7±3.8
16.9±5.70.38
Number of TACE sessions, mean±SD
1.5±0.7
1.7±0.7
1.4±0.70.18
Technique, n0.64
Selective
12
Superselective
26
PES, %
Complication, %
Follow-up (months), mean±SD
6
12
6
14
50
44.4
550.52
26.3
16.7
350.20
15.1±14
14.7±11.3 15.4±16.30.79
PVA, polyvinyl alcohol; n, number of patients; SD, standard deviation; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HCC, hepatocellular carcinoma; AST, aspartate aminotransferase; ALT, alanine aminotransferase; AFP, alpha-fetoprotein; PT, prothrombin time; TACE, transarterial chemoembolization; PES, postembolectomy syndrome.
had Child-Pugh B disease with massive
ascites and large tumor sizes exceeding
10 cm in diameter. The remaining three
patients were in the PVA group (16%
of that group); two patients had ChildPugh C and one patient had Child A
disease. One patient developed an intrahepatic abscess, which healed after
insertion of a drainage catheter. We
also observed peritonitis (n=1), pleural
effusion (n=1), ascites and encephalopathy (n=1), and transient increase in
liver enzymes (n=1) in the TACE study
group. Patients with (n=10) and without
(n=28) complications had significantly
different survival rates at 12, 24, 36, 48
and 60 months (20%, 10%, 0%, 0%, and
0% vs. 67%, 42%, 17%, 7%, and 3%;
P < 0.001). Mean survival was 11 months
in patients with complications and 20
months in patients without complications.
Survival was also analyzed in terms
of lipiodol accumulation type. Five
patients who did not have follow-up
CT due to early mortality within one
Gelfoam vs. polyvinyl alcohol in TACE of hepatocellular carcinoma • 325
month and one patient who had follow-up MRI instead of CT were exVariablesn
P
cluded from this analysis. Survival of
patients with type 1 accumulation
Liver involvement (%), ≤50/>50
33/50.820
(n=9) was significantly better than paTumor diameter (cm), ≤5/>5
23/150.946
tients with type 2, 3 or 4 accumulation
HCC foci, ≤3/>3
29/90.023a
(n=23); survival rates at 12, 24, 36, 48
Child-Pugh class, A/B/C
20/15/30.096
and 60 months were 88%, 77%, 55%,
22%, and 22% for type 1 lipiodol accuOkuda class, I/II/III
17/18/30.122
mulation and 52%, 26%, 4%, 4%, and
AST (U/L), ≤63/>63
18/200.376
4% for other types of lipiodol accumuAFP (ng/mL), ≤400/>400 31/7<0.001a
lation (P = 0.026); mean survival was
Portal vein thrombosis, yes/no
3/350.450
35 months and 15 months, respectively. The relationship between lipiodol
Embolic agent, PVA/gelfoam
18/200.235
accumulation type and selectivity of
Technique, selective/superselective
12/260.579
the TACE was significant, such that
PES, yes/no
20/180.139
superselective embolization improved
type 1 lipiodol accumulation. A similar
Complication, yes/no
10/28<0.001a
relationship was also present between
Etiology, HBV/HCV/other
18/15/50.316
type 1 lipiodol acumulation and comLipiodol accumulation type, type 1/other types
9/230.026a
plete tumor response.
Tumor response type, type 4/other types
10/230.009a
Tumor response is an important
factor of TACE success and complete
Gender, female/male
10/280.762
response is the main goal of the treatSystemic disease, yes/no
14/240.731
ment. Patients with complete response
Age (years), ≤ 60/>60
12/260.014a
(n=10) had significantly better survival
Number of TACE sessions, 1/>1
22/160.512
compared with other types of response
(n=23). Again five patients with earRFA, yes/no
4/340.400
ly mortality were excluded from this
PEI, yes/no
4/340.169
analysis. Survival rates at 12, 24, 36,
n, number of patients; HCC, hepatocellular carcinoma; AST, aspartate aminotransferase; AFP, alpha-fetopro48 and 60 months were 70%, 60%,
tein; PVA, polyvinyl alcohol; PES, postembolectomy syndrome; HBV, Hepatitis B virus; HCV, Hepatitis C virus;
50%, 30%, and 20% in patients with
TACE, transarterial chemoembolization; RFA, radiofrequency ablation; PEI, percutaneous ethanol injection.
a
P < 0.05.
complete response and 60%, 34%, 4%,
0%, and 0% for patients with other response (P = 0.009).
Older patients (>60 years, n=26) had
better survival than younger patients
1.0
(≤60 years, n=12); survival rates at 12,
24, 36, 48 and 60 months were 65%,
0.8
46%, 23%, 11%, and 7% for patients
>60 years and 33%, 16%, 0%, 0%, and
0% for patients ≤60 years (P = 0.014);
0.6
mean survival was 22 months vs. 10
months, respectively.
Survival probability
Table 2. Effect of variables on survival
0.4
0.2
0.0
0
20
40
60
80
Time (months)
Figure. Kaplan-Meier survival curve of patients who underwent transarterial
chemoembolization with polyvinyl alcohol (PVA) or gelfoam. Dashed line indicates the PVA
group; solid line represents the gelfoam group. Mean survival was 21.8±18.7 months (95%
confidence interval [CI], 13–30 months) for the PVA group and 15.9±17.9 months (95% CI,
8–23 months) for the gelfoam group.
326 • July–August 2014 • Diagnostic and Interventional Radiology
Discussion
Our results showed no significant
difference in survival of HCC patients
treated with TACE using PVA or gelfoam. Furthermore there was no significant difference between PVA and gelfoam groups in terms of complication,
postembolectomy syndrome, and the
number of TACE sessions. Complete
tumor response to treatment, type 1
lipiodol accumulation, older age (>60
years), low number of tumor foci (≤3),
and low levels of serum AFP (≤400 ng/
mL) were prognostic factors signifiKoçyiğit et al.
cantly associated with higher survival
rates. Although superselectivity of embolization was not a significant factor
on survival, it was a significant indicator of type 1 lipiodol accumulation,
and it can be speculated that selectivity indirectly improves survival.
The benefits reported in two prospective randomized controlled pilot
trials secured the role of TACE in the
treatment of HCC (5, 17). Lo et al. (17)
compared TACE (using cisplatin, lipiodol, and gelfoam) with symptomatic
treatment, and determined the survival
rates at 12, 24, and 36 months as 57%,
31%, and 26%, vs. 32%, 11%, and 3%,
respectively. Llovet et al. (5) compared
TACE (using doxorubicin, lipiodol, and
gelfoam), transarterial embolization
(TAE) (using gelfoam), and symptomatic treatment groups; TACE group had
the best survival rates at 12, 24, and 36
months (82%, 63%, and 29%) compared with TAE (75%, 50%, and 29%),
and symptomatic treatment groups
(63%, 27%, and 17%). In our study the
survival rates at 12, 24, and 36 months
were 55%, 36% and 15%. Our results
were similar with those of Lo et al.
(17), but lower than those reported by
Llovet et al. (5). This difference can be
attributed to better overall condition of
the patients in Llovet et al., with the
majority of the patients having ChildPugh A score, small tumor size and
good clinical condition.
Previous studies investigated the
effect of different chemoterapeutic
agents used in TACE on survival. Lo
et al. (17) used 30 mg of cisplatin, Llovet et al. (5) administered doxorubicin at varying doses based on serum
bilirubin levels, and Barone et al. (18)
used a mixture of 20–30 mg of doxorubicin and 6–10 mg of mitomycin C
with gelfoam. There is no clear answer
for the optimal agents or doses applied
in TACE (9). In our study, doxorubicin and lipiodol emulsion was used in
both PVA and gelfoam groups.
Embolization is an important aspect
of transarterial treatment, especially in
HCC patients, since it leads to damage
and necrosis in the tumor through arterial occlusion (19). Various embolic
agents can be used in TACE such as
coils, degradable starch microspheres,
autologous blood clot, gelfoam, PVA,
and powderized herbs (12). Autolo-
gous blood clot and gelfoam could
be used as embolizing agents with a
temporary occlusion capability on the
arteries. Since the blood clot lyses immediately after the embolization, the
chance of arterial thrombosis after
several sessions of TACE is small (20).
In a randomized trial (21), the hepatic artery remained patent for a longer
time with blood clot than with gelatin
sponge, but there was no difference in
survival. On the other hand, a permanent or semipermanent arterial occlusion with more distal obstruction can
be achieved with PVA particles, due to
their smaller size ranging from 50 to
250 µm in diameter (22) . Brown et al.
(10) defined no significant difference
in survival between gelfoam powder
group and PVA group. Furthermore
the number of TACE sessions was significantly greater in the gelatin sponge
group than in the PVA group (mean
2.2 vs. 1.6; P = 0.01). We also found
no difference in survival between the
PVA and gelfoam groups. Furthermore
no difference was found between the
gelfoam and PVA groups regarding the
number of TACE sessions (mean 1.7 vs.
1.4; P = 0.18). Brown et al. (10) used
gelfoam powder (<1 mm diameter),
while we used gelfoam particles (1–2
mm diameter) as the embolic agent
in TACE. Hence, size difference can be
the reason of low number of TACE sessions needed in the gelfoam group in
our study. Gelfoam occludes the artery
temporarily with recanalization taking
place within two weeks (23). On the
other hand, PVA is generally considered to be a permanent or semipermanent embolic agent, which is used not
only in TACE but also in other procedures such as uterine artery embolization. However, occlusion of the feeding artery for a shorter period of time
can be sufficient to achieve satisfactory
ischemia to overcome cell pumps that
normally expel the chemotherapeutic
agents, and result in sufficiently high
level of chemotherapeutics to cause
tumor necrosis (12). The duration of
vascular occlusion needed to induce
tumor necrosis is not well known. In
pathological analysis of tumors resected approximately 55 days after TACE,
gelfoam sponge led to a six-fold increase in cisplatin retention in the tumor compared with the surrounding
noncancerous liver tissue; 15 of the 20
index HCCs were completely necrotic
and the remaining five demonstrated
70%–90% necrosis (24). Moreover, not
all arteries occluded with gelfoam recanalize, and a permanent occlusion
rate is about 19% (25). This can explain the insignificant difference between gelfoam and PVA groups in the
current study.
Stuart et al. (26) used gelfoam powder as an embolic agent and reported
an overall survival time of 16 months
in 52 patients. Early (30-day) mortality rate was 17% in that trial. Brown
et al. (10) reported an overall survival
period of 17 months for both gelfoam
and PVA groups with an early mortality rate of 2% and 5%, respectively. In
our study overall survival period was
15 months for the gelfoam group and
14 months for the PVA group, with an
early mortality rate of 10% and 16%,
respectively. Early mortality rates were
similar between the gelfoam group and
the PVA group. High mortality rates
observed by Stuart et al. (26) and our
study group can be explained by the inclusion of patients with Child-Pugh C
and segmental portal vein thrombosis
in the TACE procedure. Additionally,
patients with bilobar disease were treated in two lobar infusions separated by a
few days in their study. However, most
operators performing TACE in bilobar
disease separate treatment sessions by a
minimum of four weeks (27).
Survival rates were significantly better in patients who experienced no
complications compared with patients
who had complications. This can be
explained by the duration of TACE session, tumor size and Child-Pugh class,
since high number of TACE sessions,
big tumor size and low Child-Pugh
class can increase the complication
rates. To our knowledge, no previous
study in the literature investigated the
effect of complications on survival
rates, and further studies are required
to shed more light on this issue.
In terms of the number of HCC foci,
patients with ≤3 HCC nodules had
significantly better survival rates than
patients with >3 HCC nodules. There
was also a significant relationship between the number of HCC foci and
AFP levels, since more tumor foci induce higher AFP levels, which depicts
Gelfoam vs. polyvinyl alcohol in TACE of hepatocellular carcinoma • 327
higher tumoral activity. Furthermore
high number of HCC foci means more
TACE sessions or selective embolization, thus the tumor response and
patient outcome can be affected negatively. Llad et al. (28) defined a significant relationship between the AFP
level (cutoff level, 400 ng/mL) and
survival in 143 HCC patients; a similar
relationship was also observed in our
study, where patients with AFP ≤400
ng/mL had better survival than those
with AFP >400 ng/mL. Llovet et al.
(5) stated that tumor response affects
the survival. Llad et al. (28) reported
a positive relationship between the
reduced tumor size and survival. We
also determined a significant effect
of tumor response on survival; thus,
complete response should be the main
goal in TACE for an effective treatment
and better survival. Complete tumor
response had a significant positive relationship with type 1 lipiodol accumulation and both of them influenced
survival significantly. It can be speculated that if a type 1 lipiodol accumulation is seen on unenhanced follow-up
CT after the TACE, one can expect a
better tumor response and survival. Although superselective embolization indicated type 1 lipiodol accumulation,
it had no significant effect on survival
in our study. Bouvier et al. (11) reported similar results in their retrospective
study. On the other hand, several studies revealed significant improvement
on survival with more selective techniques, and recommended the use of
these techniques in TACE for better
tumor response and patient outcome
(11, 15, 29). Age of the patient is an
important factor on tumoral invasion,
recurrence risk, metastatic potential,
survival and prognosis of disease (30).
Several studies defined better survival
rates at older ages, since younger patients have more agressive disease with
a higher grade of HCC at the time of
diagnosis (31). In our study we also observed better survival rates in patients
over 60 years of age.
This retrospective study has several
major limitations. Our study population is relatively small. Retrospective
assesment of the subjects limited the
scientific impact of the results and
did not allow the randomization of
patients. Thus, our results need to be
validated with further prospective randomized control trials on larger series.
In conclusion, using different embolic agents for TACE had no significant effect on survival. Although
PVA group had slightly better survival rates than gelfoam group, this can
be attributed to the greater number of
Child-Pugh A patients in PVA group
than in gelfoam group. Further trials
should be focused on the effect of different embolic agents on survival following TACE. Superselective technique
should be preferred in TACE for better
tumor response and improved patient
outcome. Tumor response, number of
HCC foci, patient age, serum AFP level,
lipiodol accumulation type, and complications due to TACE had a significant effect on survival in HCC treated
with TACE.
Conflict of interest disclosure
The authors declared no conflicts of interest.
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